Method and device for releasing powder

ABSTRACT

An inhaler device and a method are disclosed in which powder for inhalation is jetted off a prepared device surface containing a defined pre-metered quantity of finely divided powder. The jetting function is obtained by a directed air stream ( 16 ) having the characteristic of an air jet pushing or cutting free a medical powder applied to a carrier surface ( 10 ) and by creating a stream of air dispersing the powder into a the inspiratory air ( 3 ) at the moment it is being inhaled. An inhaler device utilizing the present method is preferably further provided with active (air permeable) porous walls ( 4 ) for further preventing finely divided powder from sticking to the inner faces of the inhaler device by creating a pressure gradient across the active wall, thus forcing a small flow of air through the active wall thereby keeping the powder from sticking to the inner faces ( 4 ).

TECHNICAL FIELD

[0001] The present invention relates to a method and a device forreleasing a finely divided powder to be inhaled and more particularly amethod and a device for releasing a medical powder from a dosing carrierconnected to an inhaler for creating a well defined and efficientlyinhaled medication dose.

BACKGROUND

[0002] Today supply and distribution of medical powders take place inmany different ways. Within health care there is rapidly growinginterest in the possibility to dose and distribute powder directly tothe lungs of a patient by means of an inhaler to obtain an efficient,fast, and patient friendly administration of the specific medicalsubstance.

[0003] In order to make certain that the medical powder to beadministered will be safely carried to the lungs of a patient, thepowder should have a grain size less than 5 μm. Large grain sizesgenerally will stick in the oral cavity and the throat, and too smallgrain sizes may follow the expiration air out.

[0004] However, powder having a small grain size will demonstrate astrong tendency to agglomerate, i.e. to clod into larger grains. In theinhalers being used today a large portion of the powder is agglomeratedwhen it is dosed and much powder therefore will stick to the upperrespiratory tracts. Different manners to de-agglomerate the powder havebeen developed and in most of the cases, inspiration air is used todisassemble the agglomerated powder. Another method wherede-agglomeration is performed by mechanical means is disclosed in forinstance the granted Swedish Patent Application No. 9802648-7 (Swedishpublication SE 512 433).

[0005] It is also common to utilize carriers having a larger grain sizeonto which the fine powder is distributed. Upon inspiration the largesize grains will then stick in the oral cavity while the small grainswill be let free and proceed to the lung. Some manufacturers alsoutilize electrically driven propellers, piezo-vibrators and/ormechanical vibration to disassemble the agglomerates. To obtain a largeportion of separate small particles in the inspiration air is thus avery important factor to achieve a high efficiency upon inhalation.

[0006] One of the problems upon inhalation of a medical powder is that arelatively large portion of the dose will also stick in the inhalerdevice. To be able to include all powder and disassemble agglomerates ahigh air velocity is needed. However, the high velocity also has anegative influence on the emitted dose, as a large portion of the powderwill stick to the walls within the inhaler. A dose given by an inhalerof today the respiratory part (grain size less than 5 μm) may often beonly 20% of the dose.

[0007] The problems are illustrated in U.S. Pat. No. 5,740,794 and WO96/09085, for example, where an apparatus and a method are demonstratedfor aerosolizing a medicament dose comprising dry powder to be suitablefor inhalation. The applied method relies on the use of pressurized gas,normally air, for dispersing and transporting the powder and separatingagglomerates into individual powder particles in the dose by using highair speeds in certain parts of the transport tube system, therebyde-agglomerating by introducing very high shear forces. Besides theinconvenience of relying on an external source of pressurized air, theevidence is far from conclusive regarding the powder retention in thepowder receptacle and the transport tube system.

[0008] In order to be able to use inhalation to provide administrationand in this manner replace injection of medicine the grain size must bevery small. For an optimal amount of substance to reach the alveoli, anadministered powder dose should preferably have an aerodynamic grainsize less than 3 μm. Besides, the inspiration must be carried out in acalm way to decrease air speed and thereby depositions in the upperrespiratory tracts.

[0009] For achieving a high respiratory dose a so-called spacer is oftenused to have the small grains evenly distributed in a container fromwhich the inhalation can take place. In principle a dosing device or aninhaler is coupled to a container having a relatively large volume andinto this container a powder or an aerosol is injected, which partly isdistributed in the air space and partly sticks to the walls. Uponinhalation from the spacer the fine powder floating free in the air willeffectively reach the alveoli. This method in principle has twodrawbacks, firstly difficulties to control the amount of medicineemitted to the lung as an uncontrolled amount of powder sticks to thewalls of the spacer and secondly difficulties in handling the relativelyspace demanding apparatus. It has been demonstrated, e.g. in U.S. Pat.No. 5,997,848 that systemic delivery of dry insulin powder can beaccomplished by oral inhalation and that the powder can be rapidlyabsorbed through the alveolar regions of the lungs. However, doseresolution still seems to be low. According to the disclosure, theinsulin doses have a total weight from a lowest value of 0.5 mg up to10-15 mg of insulin and the insulin is present in the individualparticles at from only 5% up to 99% by weight with an average size ofthe particles below 10 μm.

[0010] However, there is still a demand for a method and a devicesimplifying administration of medical powder by means of an inhalerdevice providing a compact arrangement without the need of, forinstance, a space-demanding spacer or external power sources.

SUMMARY

[0011] The present invention discloses a method and a device forefficiently obtaining by inhalation a total amount of administeredmedical powder spatially distributed in the inspiration air, preferablywithout the use of a so-called spacer.

[0012] According to the present method the powder is jetted off aprepared device surface containing a defined pre-metered quantity offinely divided powder, preferably an electro-powder constituting anelectro-dose. The jetting function is normally the result of theinhalation effort on the user's behalf, but in some cases the effort isaided by internal or external sources of power. By way of auser-actuated release mechanism, a directed air stream, having thecharacteristic of an air jet, pushes or cuts free a medical powderdeposited on the surface of a carrier member. The stream of airdisperses the powder and floats the individual particles into the airjust as it is being inhaled. An inhaler device utilizing the presentmethod is preferably further provided with active (air permeable) porouswall elements for further preventing powder grains from sticking to theinside faces of the inhaler device. The inhalation effort of the usercreates a total pressure gradient preferably in the range 1-5 kPa overthe inhaler. A part of the pressure drop is available over the activewall, thus forcing a flow of air through the active wall such that theresulting airflow prevents the floating powder particles from touchingthe inside faces.

[0013] A method according to the present invention is set forth by theindependent claim 1 and further embodiments of the present method aredefined by the dependent claims 2 to 15, and an inhaler device accordingto the present invention is set forth by the independent claim 16 andfurther embodiments of the device are defined by the dependent claims 17to 27.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The invention, together with further objects and advantagesthereof, may best be understood by referring to the followingdescription taken together with the accompanying drawings, in which:

[0015]FIG. 1 indicates in a schematic way according to the presentinvention operation of an inhaler device using a fixed carrier member;

[0016]FIG. 2 illustrates in a second alternative, according to thepresent invention, operation of the inhaler device using a rotatingcassette carrier;

[0017]FIG. 3 illustrates in a third embodiment the operation of theinhaler device using a carrier in the form of a belt;

[0018]FIG. 4 illustrates in a fourth embodiment the operation of theinhaler device using a carrier in the form of a rotating cylinder;

[0019]FIG. 5 illustrates in a fifth embodiment operation of the inhalerdevice using a moving air jet;

[0020]FIG. 6 illustrates in a sixth embodiment the inhaler device usinga single porous supporting casing using active wall elements;

[0021]FIG. 7 illustrates an embodiment of a flat carrier disc forelongated strips forming doses of powder;

[0022]FIG. 8 illustrates an embodiment of a carrier disc for spotsforming doses of powder;

[0023]FIG. 9 illustrates another embodiment of a circular carrier discpresenting radial slots to receive strips of doses of powder;

[0024]FIG. 10 illustrates an embodiment of a rotating cassettepresenting elongated strips of powder doses; and

[0025]FIG. 11 illustrates another embodiment of a rotating cassettepresenting circular elongated doses of powder;

[0026]FIG. 12 is a flow diagram illustrating the method according to thepresent invention.

DETAILED DESCRIPTION

[0027] In FIG. 1 the basic principle of the method according to thepresent invention is schematically illustrated.

[0028] An inhaler device is embodied by an illustrative casing 1 havinga mouthpiece 2 for suction of the powder to be administered to the lungsof the user. A carrier 10 in advance prepared with a pre-meteredelectro-dose 11 of finely divided powder is positioned within theinhaler casing 1. In this context a pre-metered dose is defined eitheras a merged, elongated continuous amount of finely divided powder or asone or more separate, different spots of powder, in both cases depositedon a carrier member suitable for administration in a single inhalation.This carrier surface 10 in a basic embodiment is a flat fixed carrierprovided with one or more pre-metered electro-doses 11. FIG. 7 shows anembodiment of a flat carrier 10 provided with strips of powder doses 22.FIG. 8 illustrates another embodiment of a flat carrier 18 provided withspots of powder doses 20. In the embodiment the spots are separated fromeach other by being placed in defined recesses, but they may also beplaced directly onto the surface of the carrier. FIG. 9 illustratesstill another embodiment of a flat carrier 10 in form of a circular discwith radial recesses 22 for powder doses. The powder to be dosed ispreferably positioned as strips in such recesses to have a goodseparation between doses, but the powder may of course also bepositioned as strips on an entirely flat carrier.

[0029] A pre-metered electro-dose here constitutes an active powdersubstance or a dry powder medical formulation, preferably anelectro-powder, which is metered onto a device member forming a dosecarrier, a metered dose having a fine particle fraction (FPF) presentingof the order 50% or more by mass of its content with a particle sizebelow 5 μm, the dose further presenting an optimized porosity of 75 to99,9%.

[0030] The electro-powder forms an active dry powder substance or drypowder medical formulation with a fine particle fraction (FPF)presenting of the order 50% or more of the powder by mass with anaerodynamic particle size below 5 μm and provides electrostaticproperties with an absolute specific charge per unit mass after chargingof the order 0.1 to 25 μC/g and presents a charge decay rate constantQ₅₀ of more than 0.1 s, and having a tap density of less than 0.8 g/mland a water activity aw of less than 0.5.

[0031] In FIG. 1 an air jet 16 is directed to the electro-dose 11 of thecarrier 10. This air jet blows the powder off from the carrier 10. In anillustrative embodiment a nozzle 15, positioned close to the dose ofpowder 11, forms the air jet 16. Generally a user-actuated releasemechanism requires a certain well defined but adjustable minimumpressure differential between a surrounding atmosphere and the airwaysof an inhaling person. The user actuated release mechanism usuallytriggers off the dose delivery process by opening the interior of theinhaler for a directed air-stream. The air-stream is directed by meansof a nozzle, which is designed such that it utilizes the availablepressure drop caused by the inhalation to achieve a high air speed atthe outlet near the dose to be delivered and with as little dissipativeloss as possible in the process.

[0032] When the powder has been jetted off from the carrier 10, it willautomatically be dispersed into the air above the carrier and themixture 3 of air and powder will simultaneously be sucked out through amouthpiece 2 of the inhaler casing 1. During this part of theinhalation, the inner part of the inhaler will act as a spacer, wherethe total dose will be spatially distributed in the air before cominginto the mouthpiece 2.

[0033] To prevent powder from depositing onto the inner faces of thecasing 1 which normally happens when spacers are used in inhalers oftoday, an additional active wall 4 is introduced. The principle ofactive walls is further disclosed in our Swedish Patent SE 9904484-4(Swedish Publication No. SE 513 696). Through this wall a small portionof air will pass either directly from the ambient air if the active wallis a structural element of the inhaler casing, or indirectly from aspace between the casing 1 of the inhaler device and an additional innerenclosure using active walls 4 when air is sucked out through themouthpiece 2 of the inhaler device. By choosing the optimal pressuredrops and materials in the design of the casing 1 and the active wallelements 4 optimal aerodynamic conditions are obtained to help perfectthe resulting airflow. The inhaler is generally designed for a userinduced pressure drop in the range 1-5 kPa resulting in an airflow of15-50 l/min and a low air velocity through the mouthpiece to get highestpossible amount of powder from the dose to the deep lungs.

[0034] In another embodiment, schematically illustrated in FIG. 6, theinhaler casing 1 uses integrated active porous wall elements 4 at leastpartly as necessary to let small flows of air in through the casing wallto prevent powder from depositing onto the inner faces of the inhalerduring an inhalation operation.

[0035] To jet off powder in this way from a carrier will consistentlyavoid the problems of powder sticking to the inner faces of for instancethe mouthpiece where the speed of the air-powder mixture normally isvery high and the concentration of powder is high.

[0036] In another embodiment in FIG. 2 a rotating cassette 6 replacesthe flat carrier 10. The cassette 6 contains of the order of 4 to 20electro-doses of powder and will move automatically by means of asuitable mechanical construction one step forward for each inhalation.The mechanical construction in a preferred embodiment will also includea member opening the sealed dose immediately before the inhalation. Inthis alternative, it is also possible to use a container withpressurized air combined with the cassette and to use a breath activatedelectrical motor to rotate the cassette 6. An embodiment of such acassette 6 is further demonstrated in FIG. 10 illustrating positions forelongated strips of doses 24.

[0037] In a third embodiment in FIG. 3 the carrier may constitute acarrier belt 7 giving the possibility to load a big number of doses intothe inhaler. The carrier belt has two rollers, one magazine roll 8 andone receiving roll 9. The belt is moving one step forward for eachinhalation with the help of for instance an electrical motor connectedto the receiving roll. Alternatively the belt is moving forward duringthe inhalation to get a continuous dosing of the powder.

[0038] In a fourth embodiment in FIG. 4 the powder is jetted off as afunction of time in a controlled way by the nozzle 15 from a cylinder 17provided with one or more spots or elongated strips of electro-powder.At the instance of an inhalation, the cylinder will in one alternativedo one revolution and one dose is jetted off during a set time for anoptimal inhalation. In FIG. 11 yet another embodiment of the rotatingcassette 17 indicated in FIG. 4 is demonstrated. The cassette 17 in thisembodiment presents circular elongated doses of powder 26. The inhalerthen is automatically ready for next inhalation, as the air jetautomatically will change to next strip. In another alternative, thepowder strip can also be prepared in the form of a spiral on the surfaceof the cylinder, which will make it possible to change the delivereddose by choosing from part of a resolution to several revolutions of thecylinder. In addition, in this case the inhaler is immediately ready fornext inhalation only by following the spiral strip. The flexibility withthe cylinder will give the possibility to always get the correct dosemass and the optimal time for inhalation. A thin film to avoid moisturepickup will preferably protect the powder.

[0039] The release of powder by the air jet 16 will be activated by theinspiration of the user. The air jet 16 will be a direct effect of theoutgoing air stream through the mouthpiece 2 or in another embodimentmay be indirectly started by activation of an included small containerwith pressurized air. Such a container with pressurized air may simplybe combined with the cylinder 6. It will also be possible to use abreath activated electrical motor to rotate the cylinder 17.

[0040] In a fifth embodiment in FIG. 5 a movable air jet 16, is used toblow a dose off a carrier provided with one or a number of electro-dosesarranged as one or more spots or elongated strips to get a definedrelease of powder during an inhalation operation. The carrier can be inthe form of a flat disc or a flat circular disc.

[0041] The electro-dose is jetted off in a controlled way by the nozzle15 moving along the track of powder either by moving the nozzle as shownin FIG. 5 or moving the carrier in a linear motion. The amount of powderreleased per unit time will depend on two factors, the physical form ofthe dose and the relative movement between the nozzle and the carrier.In the first case, the moving nozzle is a part of a moving wall 19,which is pushed forward as shown by the arrows by the air coming inthrough openings 12 when the inhalation starts. In this way, theinhalation time can be optimized by a correct aerodynamic constructionof the inhaler device. When moving the carrier of the other alternativethe wall 19 is fixed and the carrier 18 with the electro-powder ismoving. A breath-activated motor can alternatively perform the movementsof the nozzle or the carrier and the use of pressurized air from a smallbreath-activated container can perform blowing off powder.

[0042]FIG. 12 presents a summary of the present method starting at astep 100. In step 100 a dose carrier is arranged with at least onepre-metered dose. In a succeeding step 110 a nozzle is pointed towardsthe dose onto the dose carrier for a release of powder. Finally in astep 120 a user-actuated release mechanism is introduced for initiatingthe release of powder from the dose carrier by means of the nozzle.

[0043] It will be obvious to a person skilled in the art that thepresent inhaler device may be modified and changed in many ways withoutdeparting from the scope of the present invention, which is defined bythe appended claims

1. A method for releasing medical powder from a dose carrier memberconnected to an inhaler device for creating a well-defined and spatiallydistributed mixing of air and medical powder, comprising the steps ofarranging a dose carrier member provided with at least one pre-metereddose of finely divided powder to be administered by means of inhalation;pointing a nozzle towards the dose deposited on the dose carrier memberfor releasing the powder; and introducing a user-actuated releasemechanism, which initiates a concentrated, high-speed air jet releasingand dispersing the powder of a dose.
 2. The method according to claim 1,comprising the further step of applying active wall elements asstructural members in a supporting casing containing the dose carriermember, whereby said active wall elements prevent powder from stickingonto inside faces of the inhaler device by letting air free from powderinto the supporting casing.
 3. The method according to claim 1,comprising the further step of arranging a solid supporting casing withan additional inner enclosure using active walls containing said dosecarrier member, whereby said active walls prevent powder from stickingonto inside faces by letting in air, free from powder, from a spacebetween a porous wall enclosure and the supporting casing.
 4. The methodaccording to claim 1, comprising the further step of arranging thenozzle in close proximity to a selected dose and further introducing avalve mechanism, which opens for the air jet through the nozzle in orderto release a certain part or all of the powder of a selected pre-metereddose into the inspiratory air of a person sucking air through amouthpiece of the inhaler device.
 5. The method according to claim 1,comprising the further step of limiting the necessary user-inducedpressure drop across the inhaler for an acceptable delivery of the dosewithin a range 1-5 kPa and more preferably 1-3 kPa.
 6. The methodaccording to claim 1, comprising the further step of introducing arelative motion between said dose carrier member and said air jet inorder to release a certain part or all of the powder of a selectedpre-metered dose into the inspiratory air of a person sucking airthrough a mouthpiece of the inhaler device.
 7. The method according toclaim 1, comprising the further step of arranging said dose carriermember as a flat disc member provided with elongated strips ofpre-metered doses of powder.
 8. The method according to claim 1,comprising the further step of arranging said dose carrier member as aflat disc member provided with pre-metered doses of powder, each dosemade up of one or more spots of powder.
 9. The method according to claim1, comprising the further step of arranging said dose carrier member asa flat circular disc member provided with elongated radial strips ofpre-metered doses of powder.
 10. The method according to claim 1,comprising the further step of arranging said dose carrier member as aflat circular disc member provided with pre-metered doses of powder,each dose made up of one or more spots of powder in a radialarrangement.
 11. The method according to claim 1, comprising the furtherstep of arranging said dose carrier member as a cylinder provided withelongated strips of pre-metered doses of powder.
 12. The methodaccording to claim 1, comprising the further step of arranging said dosecarrier member as a cylinder provided with pre-metered doses of powder,each dose made up of one or more spots of powder in a straight orcircular arrangement on its lateral area.
 13. The method according toclaim 1, comprising the further step of moving a carrier belt providedwith elongated strips of pre-metered doses of powder past a supportpositioned between a carrier belt magazine roll and a carrier beltreceiving roll.
 14. The method according to claim 1, comprising thefurther step of initiating a powder releasing air jet by a suction ofair through a mouthpiece of an inhaler casing containing a powder dosecarrier.
 15. The method according to claim 1, comprising the furtherstep of providing said at least one pre-metered dose on said dosecarrier member as electro-dose made up of electro-powder.
 16. An inhalerdevice for administering medical powder from a dose carrier connected toan inhaler device for creating a well-defined and evenly distributedmixing of air and medical powder for an inhalation operation, wherein adose carrier member contains at least one pre-metered dose of powder forinhalation purposes; a casing forms a main portion of an inhaler devicecontaining a mouthpiece for sucking air through inlet openings andthrough the inhaler device; an inner member forming a nozzle is directedtowards a selected pre-metered dose of finely divided powder depositedonto a selected area of said dose carrier member; a user-actuatedrelease mechanism initiates upon inhalation a powerful, high-speed airjet through the nozzle thereby releasing and dispersing efficiently themedical powder of said pre-metered dose from said dose carrier memberinto the air being inhaled, thereby forming a well-defined and welldistributed mix of air and medical powder during an inhalationoperation; one or more active porous wall elements either integrateddirectly in the inhaler casing or forming an inner enclosure inside theinhaler casing prevents powder from depositing onto inside faces of theinhaler device when sucking air through the inhaler device, therebymaintaining a well-defined and well distributed mix of air and medicalpowder during an inhalation operation.
 17. The inhaler device accordingto claim 16, wherein a relative motion is performed between a createdair-jet and said dose carrier member, in order to release a certain partor all of the powder of a selected pre-metered dose to get a definedrelease as a function of time of powder into the inspiratory air of aperson sucking air through a mouthpiece of the inhaler device.
 18. Theinhaler device according to claim 16, wherein said dose carrier memberis a flat disc member provided with elongated strips of pre-metereddoses of powder.
 19. The inhaler device according to claim 6, whereinsaid dose carrier member is a flat disc member provided with pre-metereddoses of powder, each dose made up of one or more spots of powder. 20.The inhaler device according to claim 16, wherein said dose carriermember is a flat circular disc provided with elongated radial strips ofpre-metered doses of powder.
 21. The inhaler device according to claim16, wherein said dose carrier member is a flat circular disc memberprovided with pre-metered doses of powder, each dose made up of one ormore spots of powder in a radial arrangement.
 22. The inhaler deviceaccording to claim 16, wherein said dose carrier member is a cylinderprovided with elongated strips of pre-metered doses of powder.
 23. Theinhaler device according to claiml6, wherein said dose carrier member isa cylinder provided with elongated strips of pre-metered doses ofpowder, each dose made up of one or more spots of powder in a straightor circular arrangement on the lateral area.
 24. The inhaler deviceaccording to claim 16, wherein said dose carrier member is a carrierbelt provided with elongated strips of pre-metered doses of powder andwhich belt dose by dose passes a support between a carrier belt magazineroll and a carrier belt receiving roll.
 25. The inhaler device accordingto claim 16, wherein said air jet is created by means of an air-streaminitiated from an additional container with pressurized air.
 26. Theinhaler device according to claim 16, wherein necessary user-inducedpressure drop across the inhaler for an acceptable delivery of thepowder dose is limited to a range 1-5 kPa and more preferably 1-3 kPa.27. The inhaler device according to claim 16, wherein at least onepre-metered dose deposited on the dose carrier member is as electro-dosemade up of electro-powder.